Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many skin disorders, such as atopic dermatitis and psoriasis, worsen during stress and are associated with increased numbers and activation of mast cells which release vasoactive, nociceptive, and proinflammatory mediators. Nontraumatic acute psychological stress by immobilization has been shown to induce mast cell degranulation in the rat dura and colon. Moreover, intradermal injection of corticotropin-releasing hormone (CRH) or its analogue urocortin (10(-5)-10(-7) M) induced skin mast cell degranulation and increased vascular permeability. Here, we investigated the effect of acute immobilization stress on skin mast cell degranulation by light microscopy and electron microscopy. Immobilization for 30 min resulted (P < 0.05) in degranulation of 40.7 +/- 9.1% of skin mast cells compared to 22.2 +/- 7.3% in controls killed by CO(2) or 17.8 +/- 2.4% in controls killed by pentobarbital. Pretreatment intraperitoneally (ip) with antiserum to CRH for 60 min prior to stress reduced (P < 0.05) skin mast cell degranulation to 21.0 +/- 3. 3%. Pretreatment with the neurotensin (NT) receptor antagonist SR48692 reduced (P < 0.05) mast cell degranulation to 12.5 +/- 3.4%, which was significantly (P < 0.05) below control levels. In animals treated neonatally with capsaicin to deplete their sensory neurons of their neuropeptides, such as substance P (SP), mast cell degranulation due to immobilization stress was reduced to about 15%. This is the first time that stress has been shown to trigger skin mast cell degranulation, an action not only dependent on CRH, but apparently also involving NT and SP. These findings may have implications for the pathophysiology and possible therapy of neuroinflammatory skin disorders such as atopic dermatitis, neurogenic pruritus, or psoriasis, which are induced or exacerbated by stress.
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PMID:Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: A link to neurogenic skin disorders. 1046 24

Seasonal allergic conjunctivitis is rarely associated with permanent vision impairment; however, it is a relatively common condition that may compromise the quality of life. It may, in extreme cases, impair daily activities, including work. Numerous treatment options have become available for the relief of acute symptoms. Avoidance should always be the first line in therapy but, in most cases, is not practical, especially with pollen allergies. The use of saline eyedrops is simple and nontoxic, and it is effective in up to 30% to 35% of cases. It can and should be added to all other remedies to reduce adverse effects and cost by decreasing the need for other therapeutic options. Antihistamines and decongestants are useful treatment choices for the majority of cases. Ketorolac tromethamine may be helpful in relieving pruritus, but it offers little advantage over topical antihistamines. Corticosteroids may be used for severe cases for a limited time. If topical corticosteroids are being considered, an ophthalmologist should be consulted. Cromolyn sodium and lodoxamide ophthalmic solution may be helpful in the prophylaxis of symptoms during the allergy season, but these agents require frequent dosing. Olopatadine hydrochloride is a mast cell stabilizer and antihistamine that can be dosed twice a day. Immunotherapy is effective and should be offered to those who are intolerant or have allergic conjunctivitis refractory to medications.
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PMID:Seasonal allergic conjunctivitis: overview and treatment update. 1047 15

Two assays have been done to evaluate the effect of immunotherapy in nasal allergy. First, a trial of nasal immunotherapy and second, the study of mediator release after vaccines. Local immunotherapy, applied directly, triggers different response mechanisms. Specific nasal immunotherapy started before seasonal or perennial symptoms peak, has been done by increasing the doses of allergen three times a week during a 3-month period and a manutention period of a weekly nasal puff of the same allergen. Symptom scores and drug consumption have been registered. The results have been compared with the scores obtained in the same patients over the same period of the same year before immunotherapy. In perennial rhinitis blockage, rhinorrea, sneezing and itching scores all decreased. In seasonal rhinitis, a similar score decrease was obtained for blockage, rhinorrea, sneezing and itching. Pharmacological scores also decreased. These data point to a short-term effect of nasal immunotherapy. Tryptase release has been evaluated in nasal washings after nasal challenge with a Parietaria (Pellitory wall) extract before and after specific systemic immunotherapy, in order to evaluate changes in mast cells reactivity. Eight patients were studied, all allergic to Parietaria. Nasal provocation tests have been done before the season with increasing doses of 10, 100 and 1000 PNU and tryptase assayed in nasal washings at 10, 20 and 30 min after provocation. Immunotherapy decreased tryptase release after nasal challenge. The data point to the effect of systemic specific immunotherapy on mast cell reactivity.
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PMID:Local and systemic immunotherapy in nasal allergy. 1057 7

Solitary mastocytoma in infants is an uncommon disease which is characterized by mast cell hyperplasia and release of mast cell mediators. The most common presentation is pruritus. The treatment of solitary mastocytoma is symptomatic. Cutaneous mastocytoma tend to resolve by adulthood.
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PMID:Solitary mastocytoma in an infant - case report with review of literature. 1069 46

While histamine is the crucial mediator of pruritus in type 1 allergic reactions, its role in atopic dermatitis (AD) is unclear. In this study, the role of mast cell mediators in protein extravasation and pruritus was evaluated using intradermal microdialysis. The microdialysis capillaries were used to apply the mast cell degranulating substance compound 48/80 (C48/80; 0.05%) or histamine (0.01%) and also to deliver H1-blockers (cetirizine, 200 microg mL-1) in nine AD patients and nine controls. Large pore size membranes (3000 kDa) enabled simultaneous analysis of protein extravasation. Itch sensation was measured psychophysically and weal and flare reaction were evaluated planimetrically. Protein extravasation induced by histamine and C48/80 was significantly reduced in AD patients. Blockade of H1-receptors by cetirizine significantly reduced C48/80-induced protein extravasation in AD patients and controls to an identical level. C48/80-induced pruritus was abolished by cetirizine in controls, whereas pruritus in AD patients was unchanged after H1 blockade. We conclude that mast cell mediators others than histamine are involved in C48/80-induced pruritus in AD patients. Whether the reduced capacity of AD patients to induce protein extravasation is of pathophysiological relevance for pruritus remains to be established.
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PMID:Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study. 1084 27

Histamine remains the main mediator released by both specific allergic and non-specific mast cell activation. Histamine is the classic mediator of itching, flare and redness. The effects of histamine in allergic conjunctivitis are mediated by H1-receptor activation on blood vessels and nociceptive nerves. Histamine effects may be prolonged and exaggerated since a defect in the histaminase enzymes has been recently demonstrated in VKC. The effects of histamine on conjunctival tissues may be more complex than those manifested by the simple symptom of itching. In fact, proinflammatory effects of histamine on conjunctival epithelial cells and fibroblasts have been demonstrated. Preliminary results showed that the H1 antagonist, emedastine, reduces significantly cytokine production from histamine-stimulated fibroblasts.
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PMID:Role of histamine in allergic conjunctivitis. 1105 44

It is suggested that mast cell is implicated to play a role in the pathogenesis of psoriasis. In this study, to determine the role of stem cell factor (SCF), which is a growth factor of mast cells, we have examined the immunohistochemical localization and serum level of SCF in patients with psoriasis vulgaris. Immunohistochemical analysis revealed diffuse staining for SCF on keratinocytes in acanthotic epidermis in psoriasis, along with endothelial cells and fibroblasts. Serum SCF level, which was measured by enzyme-linked immunosorbent assay (ELISA), was significantly increased in patients with psoriasis vulgaris (1033+/-334 pg/ml) (n=24) than that of normal subjects (666+/-196 pg/ml) (n=15) (P<0.05). However, serum SCF did not show a correlation with the disease severity assessed by psoriasis activity and severity index (PASI) score. As patients with psoriasis vulgaris occasionally complain itching, next we divided 20 patients into two groups, those with itching (Group I) (n=8) and those without (Group II) (n=12), and compared the mast cell number located in the papillary dermis between thickened psoriatic epidermis, serum SCF and plasma histamine levels. Results showed that mast cell numbers (56.3+/-22.3/mm(2) in Group I vs 31.5+/-10. 3/mm(2) in Group II, P<0.05) and plasma histamine level (1.5+/-0.59 ng/ml vs 0.39+/-0.15 ng/ml, P<0.01) were significantly higher in patients of Group I than those of patients of Group II, however, the difference of serum SCF level (1132+/-368 pg/ml vs 890+/-373 pg/ml) did not reach a statistical significance. Finally, in a separate experiment, we examined whether exogenous SCF is capable of inducing psoriatic architecture on the transplanted uninvolved psoriatic skin onto severe combined immunodeficient (SCID) mice. SCF injection for 2 weeks could not induce a psoriasiform architecture such as acanthosis on the transplanted uninvolved psoriatic skin, although mast cells were increased in number. These results raised a possibility that keratinocyte-derived SCF plays a role, in part, in the increased number of mast cells in the papillary dermis of psoriasis, which may lead pruritus associated with psoriasis. Elevated serum SCF level may also be responsible for increment of mast cells in psoriasis vulgaris. Mast cell-derived factor stimulated by exogenous SCF could not induce psoriatic epidermis, suggesting that other factors such as activated lymphocytes or macrophages are further required for the development of psoriatic lesions.
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PMID:Possible contribution of stem cell factor in psoriasis vulgaris. 1108 98

Upon activation nociceptors release neuropeptides in the skin provoking vasodilation and plasma protein extravasation in rodents, but only vasodilation in humans. Pivotal peptides in the induction of neurogenic inflammation comprise calcitonin gene-related peptide and substance P, the latter being suggested to act partly via degranulation of mast cells. In this study substance P and calcitonin gene-related peptide-induced vasodilation, protein extravasation, histamine release, and sensory effects were investigated simultaneously in human skin by dermal microdialysis. The vasodilatory prostaglandin E(2) and the mast cell activator codeine served as positive controls. Substance P and calcitonin gene-related peptide applied intradermally via large cut-off plasmapheresis capillaries induced dose-dependent local vasodilation, but only SP provoked protein extravasation in concentrations greater than 10(-9) M. Substance P-induced (10(-8)-10(-6) M) protein extravasation was not accompanied by histamine release and was unaffected by cetirizine (histamine H1 blocker, 200 microg per ml). Only the highest concentration of substance P (10(-5) M) induced significant histamine release. Neither neuropeptide caused any axon reflex erythema or any itch or pain sensation, whereas mast cell degranulation by codeine dose dependently provoked itch, flare, protein extravasation, and histamine release. In human skin calcitonin gene-related peptide and substance P induce vasodilation by a mechanism not involving histamine. No evidence for neuropeptide-induced activation of nociceptors was obtained. Our results suggest that endogenous calcitonin gene-related peptide and substance P have no acute sensory function in human skin. The lack of neurogenic protein extravasation in humans can most probably be attributed to low local concentrations of this neuropeptide still sufficient to exert trophic and immunomodulatory effects (10(-11) M), but too low to induce protein extravasation (10(-8) M) or even mast cell degranulation (10(-5) M). J Invest Dermatol 115:1015-1020 2000
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PMID:Acute effects of substance P and calcitonin gene-related peptide in human skin--a microdialysis study. 1112 Nov 35

We have investigated the mediators and mechanisms underlying the vasodilator effects of the potent vasoactive peptide, endothelin-1 (ET-1) and its isomers ET-2 and ET-3 in human skin, in vivo, using cutaneous microdialysis to quantify the release of mediators within the dermal response and scanning laser Doppler imaging to measure changes in blood flux. The effects of local anaesthesia, inhibition of nitric oxide synthase (NOS) by L-NAME and ET receptor blockade on the ET-induced vascular response were also investigated. ET-1, -2 and -3 all caused a dose-dependent area of pallor surrounded by a long-lasting flare which was accompanied by a short-lived burning pruritus. The concentration of nitric oxide (NO) in dialysate collected within the pallor response to 5 microM ET-1 (1.43 +/- 0.64 microM, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 +/- 0.38 microM) whilst that in the flare increased to reach a peak value of 2.28 +/- 0.61 microM at between 4 and 10 min after intradermal injection (P < 0.004). Pretreatment with local anaesthetic slowed the development of the flare and significantly reduced its size by up to 52% at 20 min after injection (P < 0.05) but had no significant effect on the central pallor. L-NAME, delivered by dialysis also caused a significant reduction in the ET-1-induced flare (P < 0.005). Bosentan, the non-selective ET(A)/ET(B) antagonist, when given by dialysis at the site of injection, reduced the area of both the ET-1-induced pallor and surrounding flare by 41 and 26%, respectively. No significant increase in tissue histamine was measured within either the pallor or flare response to ET-1, -2 or -3. Together these data confirm that the vasodilator response to endothelin-1 in human skin is neurogenic in origin and that it is in part mediated by the local release of nitric oxide. There appears to be little evidence for the involvement of mast cell-derived histamine in the initiation or modulation of ET-induced vasodilatation, in vivo.
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PMID:The neurogenic vasodilator response to endothelin-1: a study in human skin in vivo. 1118 78

Allergic eye disease is a common clinical problem adversely affecting the quality of life for millions of sufferers. This ocular process is associated with IgE-mediated conjunctival inflammation leading to signs of immediate hypersensitivity including redness, itching, and tearing. Pathologic studies have shown that the conjunctiva contains mast cells that when sensitized with IgE antibody and exposed to environmental allergens can release mediators of allergic inflammation. The type, release kinetics, and concentration of these mediators in the conjunctiva have not been completely characterized. The ability to isolate and purify mast cells and epithelial cells from human conjunctival tissue has permitted the study of mediator release and cell-to-cell signaling in this tissue. Our laboratory has developed in vitro and in vivo models to better understand how inflammatory cells are recruited to and infiltrate conjunctival tissues. These models demonstrate that mast cell activation may supply sufficient cytokine signaling to initiate and direct the well-orchestrated trafficking of eosinophils to the ocular surface, facilitate their adhesion, and cause release of potent mediators of ocular inflammation.
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PMID:Conjunctival mast cells in ocular allergic disease. 1142 71


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